NZ588353A - Limk2 inhibitors, compositions comprising them, and methods of their use - Google Patents
Limk2 inhibitors, compositions comprising them, and methods of their useInfo
- Publication number
- NZ588353A NZ588353A NZ588353A NZ58835309A NZ588353A NZ 588353 A NZ588353 A NZ 588353A NZ 588353 A NZ588353 A NZ 588353A NZ 58835309 A NZ58835309 A NZ 58835309A NZ 588353 A NZ588353 A NZ 588353A
- Authority
- NZ
- New Zealand
- Prior art keywords
- mmol
- methyl
- compound
- pyrrolo
- piperidine
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title description 80
- 238000000034 method Methods 0.000 title description 24
- 239000003112 inhibitor Substances 0.000 title description 18
- 101150017415 Limk2 gene Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 176
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 38
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- 208000035475 disorder Diseases 0.000 claims abstract description 14
- 150000003839 salts Chemical class 0.000 claims abstract description 14
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- -1 alkylheterocycle Chemical group 0.000 claims description 79
- 125000000217 alkyl group Chemical group 0.000 claims description 29
- 125000003118 aryl group Chemical group 0.000 claims description 28
- 125000000623 heterocyclic group Chemical group 0.000 claims description 25
- 239000001257 hydrogen Substances 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 22
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 20
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- 150000002367 halogens Chemical class 0.000 claims description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 5
- 239000007788 liquid Substances 0.000 claims description 5
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 4
- 125000003107 substituted aryl group Chemical group 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims 5
- PWPNYABQEOGNNC-UHFFFAOYSA-N [3-[[4-(aminomethyl)-1-(5-methyl-7h-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]phenyl] n,n-dimethylcarbamate Chemical compound CN(C)C(=O)OC1=CC=CC(NC(=O)C2(CN)CCN(CC2)C=2C=3C(C)=CNC=3N=CN=2)=C1 PWPNYABQEOGNNC-UHFFFAOYSA-N 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- KDOPAZIWBAHVJB-UHFFFAOYSA-N 5h-pyrrolo[3,2-d]pyrimidine Chemical compound C1=NC=C2NC=CC2=N1 KDOPAZIWBAHVJB-UHFFFAOYSA-N 0.000 abstract 1
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- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 88
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- UPBRQYOKPRIOPO-UHFFFAOYSA-N tert-butyl 4-[[3-(dimethylcarbamoyloxy)phenyl]carbamoyl]-4-(methoxymethyl)piperidine-1-carboxylate Chemical compound C=1C=CC(OC(=O)N(C)C)=CC=1NC(=O)C1(COC)CCN(C(=O)OC(C)(C)C)CC1 UPBRQYOKPRIOPO-UHFFFAOYSA-N 0.000 description 1
- VCPZEDYAMQQYKL-UHFFFAOYSA-N tert-butyl 4-[[3-(dimethylcarbamoyloxy)phenyl]carbamoyl]-4-methylpiperidine-1-carboxylate Chemical compound CN(C)C(=O)OC1=CC=CC(NC(=O)C2(C)CCN(CC2)C(=O)OC(C)(C)C)=C1 VCPZEDYAMQQYKL-UHFFFAOYSA-N 0.000 description 1
- OYLUTMVKYYJXLI-UHFFFAOYSA-N tert-butyl 4-[[3-(dimethylcarbamoyloxy)phenyl]carbamoyl]-4-phenylmethoxypiperidine-1-carboxylate Chemical compound CN(C)C(=O)OC1=CC=CC(NC(=O)C2(CCN(CC2)C(=O)OC(C)(C)C)OCC=2C=CC=CC=2)=C1 OYLUTMVKYYJXLI-UHFFFAOYSA-N 0.000 description 1
- OWSRDYJITUNTQR-UHFFFAOYSA-N tert-butyl 4-methyl-4-[(3-sulfamoylphenyl)carbamoyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1(C)C(=O)NC1=CC=CC(S(N)(=O)=O)=C1 OWSRDYJITUNTQR-UHFFFAOYSA-N 0.000 description 1
- MIKZCGNXDOJRGG-UHFFFAOYSA-N tert-butyl 4-methyl-4-[[3-(1,3-oxazol-5-yl)phenyl]carbamoyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1(C)C(=O)NC1=CC=CC(C=2OC=NC=2)=C1 MIKZCGNXDOJRGG-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 1
- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 239000006211 transdermal dosage form Substances 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000008136 water-miscible vehicle Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/10—Ophthalmic agents for accommodation disorders, e.g. myopia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Ophthalmology & Optometry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Oncology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Communicable Diseases (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US4660208P | 2008-04-21 | 2008-04-21 | |
| PCT/US2009/041126 WO2009131940A1 (en) | 2008-04-21 | 2009-04-20 | Limk2 inhibitors, compositions comprising them, and methods of their use |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ588353A true NZ588353A (en) | 2011-10-28 |
Family
ID=40785538
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ588353A NZ588353A (en) | 2008-04-21 | 2009-04-20 | Limk2 inhibitors, compositions comprising them, and methods of their use |
Country Status (17)
| Country | Link |
|---|---|
| US (2) | US8193202B2 (de) |
| EP (2) | EP2674433A1 (de) |
| JP (1) | JP5575110B2 (de) |
| KR (2) | KR101706391B1 (de) |
| CN (1) | CN101565420B (de) |
| AR (1) | AR071833A1 (de) |
| AU (1) | AU2009239500B2 (de) |
| CA (1) | CA2721919C (de) |
| CL (1) | CL2009000957A1 (de) |
| CO (1) | CO6321266A2 (de) |
| EA (1) | EA019488B1 (de) |
| IL (1) | IL208483A (de) |
| MX (1) | MX2010011450A (de) |
| NZ (1) | NZ588353A (de) |
| TW (1) | TW200948814A (de) |
| WO (1) | WO2009131940A1 (de) |
| ZA (1) | ZA201007129B (de) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009131940A1 (en) | 2008-04-21 | 2009-10-29 | Lexicon Pharmaceuticals, Inc. | Limk2 inhibitors, compositions comprising them, and methods of their use |
| JP2013518048A (ja) | 2010-01-22 | 2013-05-20 | レクシコン ファーマシューティカルズ インコーポレイテッド | 眼の疾患及び障害の治療のための５−（１ｈ−ピラゾール−５−イル）チアゾール系化合物 |
| TW201302754A (zh) * | 2010-11-05 | 2013-01-16 | Lexicon Pharmaceuticals Inc | ３－（４－（胺甲基）－１－（５－甲基－７ｈ－吡咯［２，３－ｄ］嘧啶－４－基）哌啶－４－甲醯胺基）苯基二甲基胺基甲酸酯之固態形式 |
| US20130253037A1 (en) * | 2010-11-16 | 2013-09-26 | Purdue Research Foundation | Aurora a kinase effectors |
| WO2012080735A1 (en) | 2010-12-16 | 2012-06-21 | Convergence Pharmaceuticals Limited | Ask1 inhibiting pyrrolopyrimidine derivatives |
| WO2012131297A1 (en) | 2011-03-28 | 2012-10-04 | Jonathan Bayldon Baell | Pyrido [3',2' :4,5] thieno [3, 2-d] pyrimidin- 4 - ylamine derivatives and their therapeutical use |
| WO2013138463A1 (en) | 2012-03-14 | 2013-09-19 | University Of Central Florida Research Foundation, Inc. | Neurofibromatoses therapeutic agents and screening for same |
| EP2867201A1 (de) * | 2012-06-28 | 2015-05-06 | Ramot at Tel-Aviv University Ltd. | Lim-kinaseinhibitoren |
| WO2014039714A2 (en) * | 2012-09-06 | 2014-03-13 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
| WO2015025172A1 (en) * | 2013-08-22 | 2015-02-26 | Mark David Charles | 5-aryl-thiazol-2-yl-amine compounds and their therapeutic use |
| WO2015150337A1 (en) | 2014-04-01 | 2015-10-08 | Amakem Nv | Lim kinase inhibitors |
| US20220288082A1 (en) * | 2019-09-25 | 2022-09-15 | Macquarie University | Treatment of dementia |
| KR102337947B1 (ko) * | 2020-02-25 | 2021-12-10 | 지니너스 주식회사 | 신장암 환자의 예후 예측을 위한 limk2의 용도 |
Family Cites Families (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4136173A (en) | 1977-01-31 | 1979-01-23 | American Home Products Corp. | Mixed xanthan gum and locust beam gum therapeutic compositions |
| US4936825A (en) * | 1988-04-11 | 1990-06-26 | Ungerleider Bruce A | Method for reducing intraocular pressure caused by glaucoma |
| US5753664A (en) | 1995-03-16 | 1998-05-19 | Takeda Chemical Industries, Ltd. | Heterocyclic compounds, their production and use |
| US6686366B1 (en) | 1998-06-02 | 2004-02-03 | Osi Pharmaceuticals, Inc. | Compounds specific to adenosine A3 receptor and uses thereof |
| PA8474101A1 (es) | 1998-06-19 | 2000-09-29 | Pfizer Prod Inc | Compuestos de pirrolo [2,3-d] pirimidina |
| KR100600550B1 (ko) | 2000-10-20 | 2006-07-13 | 에자이 가부시키가이샤 | 질소 함유 방향환 유도체 |
| JP2005501528A (ja) | 2001-06-05 | 2005-01-20 | エクセリクシス・インコーポレイテッド | ｐ５３経路のモディファイヤーとしてのＧＦＡＴｓおよび使用方法 |
| WO2003022214A2 (en) | 2001-09-06 | 2003-03-20 | Millennium Pharmaceuticals, Inc. | Piperazine and homopiperazine compounds |
| SE0201980D0 (sv) | 2002-06-24 | 2002-06-24 | Astrazeneca Ab | Novel compounds |
| AU2003302377A1 (en) | 2002-11-27 | 2004-06-18 | Santen Pharmaceutical Co., Ltd. | Remedy for glaucoma containing lim kinase inhibitory compound as active ingredient |
| US7253166B2 (en) | 2003-04-22 | 2007-08-07 | Irm Llc | 6-phenyl-7H-pyrrolo[2,3-d]pyrimidine compounds that induce neuronal differentiation in embryonic stem cells |
| TWI336257B (en) | 2003-06-13 | 2011-01-21 | Alcon Inc | Ophthalmic compositions containing a synergistic combination of three polymers |
| WO2005020921A2 (en) | 2003-08-29 | 2005-03-10 | Exelixis, Inc. | C-kit modulators and methods of use |
| US7326712B2 (en) | 2003-10-14 | 2008-02-05 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Substituted tricyclic compounds as protein kinase inhibitors |
| NZ547327A (en) * | 2003-11-21 | 2009-08-28 | Array Biopharma Inc | AKT protein kinase inhibitors |
| CA2563699C (en) | 2004-04-23 | 2014-03-25 | Exelixis, Inc. | Kinase modulators and method of use |
| MY179032A (en) * | 2004-10-25 | 2020-10-26 | Cancer Research Tech Ltd | Ortho-condensed pyridine and pyrimidine derivatives (e.g.purines) as protein kinase inhibitors |
| EP1810396A1 (de) | 2004-11-05 | 2007-07-25 | Labofa Munch A/S | Antriebsmechanismus zum herauf- und herabfahren einer tischoberfläche |
| DK176311B1 (da) | 2004-11-08 | 2007-07-23 | Ecco Sko As | Sko og fremgangsmåde til fremstilling af sko |
| DE102004058683A1 (de) | 2004-12-06 | 2006-06-14 | Robert Bosch Gmbh | Streulichtblende zur Reduzierung des in eine Kamera fallenden Streulichts |
| US20060178388A1 (en) | 2005-02-04 | 2006-08-10 | Wrobleski Stephen T | Phenyl-substituted pyrimidine compounds useful as kinase inhibitors |
| WO2006091450A1 (en) * | 2005-02-18 | 2006-08-31 | Lexicon Genetics Incorporated | 4-piperidin-1-yl-7h-pyrrolo[2,3-d]pyrimidine compounds |
| WO2007125315A2 (en) | 2006-04-25 | 2007-11-08 | Astex Therapeutics Limited | Pharmaceutical compounds |
| WO2007125321A2 (en) | 2006-04-25 | 2007-11-08 | Astex Therapeutics Limited | Purine and deazapurine derivatives as pharmaceutical compounds |
| EP2029592A1 (de) | 2006-04-25 | 2009-03-04 | Astex Therapeutics Limited | Pharmazeutische verbindungen |
| US20090082370A1 (en) | 2006-04-25 | 2009-03-26 | Neil Thomas Thompson | Pharmaceutical Combinations of PK Inhibitors and Other Active Agents |
| US7918831B2 (en) | 2006-10-12 | 2011-04-05 | Colorado Catheter Company, Inc. | Catheter assembly having protective sheath |
| WO2008048024A1 (en) | 2006-10-20 | 2008-04-24 | Electronics And Telecommunications Research Institute | Sensor signal processor apparatus |
| NZ576291A (en) | 2006-10-23 | 2011-10-28 | Lexicon Pharmaceuticals Inc | Process for preparing 5-alkyl-7h-pyrrolo[2,3-d]pyrimidine-2-ols |
| AR064416A1 (es) * | 2006-12-21 | 2009-04-01 | Cancer Rec Tech Ltd | Derivados de purina, piridina y pirimidina condensadas con heterociclos, moduladores de pka y/o pkb, composiciones farmaceuticas que los contienen, y usos para el tratamiento de enfermedades hiperproliferativas. |
| AR064415A1 (es) * | 2006-12-21 | 2009-04-01 | Cancer Rec Tech Ltd | Derivados de pirrolo-piperidinas y purinas,composiciones farmaceuticas que los contienen y usos en trastornos y/o enfermedades mediadas por pka y pkb. |
| CA2695857C (en) | 2007-08-08 | 2015-08-04 | Lexicon Pharmaceuticals, Inc. | Kinase inhibitors, compositions comprising them, and methods of their use |
| WO2009131940A1 (en) | 2008-04-21 | 2009-10-29 | Lexicon Pharmaceuticals, Inc. | Limk2 inhibitors, compositions comprising them, and methods of their use |
-
2009
- 2009-04-20 WO PCT/US2009/041126 patent/WO2009131940A1/en active Application Filing
- 2009-04-20 AU AU2009239500A patent/AU2009239500B2/en active Active
- 2009-04-20 KR KR1020107023420A patent/KR101706391B1/ko active IP Right Grant
- 2009-04-20 EP EP13178589.1A patent/EP2674433A1/de not_active Withdrawn
- 2009-04-20 EA EA201071224A patent/EA019488B1/ru not_active IP Right Cessation
- 2009-04-20 EP EP09735629.9A patent/EP2297153B1/de active Active
- 2009-04-20 JP JP2011505253A patent/JP5575110B2/ja active Active
- 2009-04-20 KR KR1020167030113A patent/KR20160129909A/ko not_active Application Discontinuation
- 2009-04-20 MX MX2010011450A patent/MX2010011450A/es active IP Right Grant
- 2009-04-20 CA CA2721919A patent/CA2721919C/en active Active
- 2009-04-20 NZ NZ588353A patent/NZ588353A/en unknown
- 2009-04-20 US US12/426,661 patent/US8193202B2/en active Active
- 2009-04-21 TW TW098113230A patent/TW200948814A/zh unknown
- 2009-04-21 AR ARP090101402A patent/AR071833A1/es unknown
- 2009-04-21 CN CN200910136811.3A patent/CN101565420B/zh active Active
- 2009-04-21 CL CL2009000957A patent/CL2009000957A1/es unknown
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2010
- 2010-10-05 IL IL208483A patent/IL208483A/en active IP Right Grant
- 2010-10-06 ZA ZA2010/07129A patent/ZA201007129B/en unknown
- 2010-11-11 CO CO10141442A patent/CO6321266A2/es not_active Application Discontinuation
-
2012
- 2012-06-01 US US13/486,122 patent/US8450332B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| AR071833A1 (es) | 2010-07-21 |
| EP2674433A1 (de) | 2013-12-18 |
| JP5575110B2 (ja) | 2014-08-20 |
| EA019488B1 (ru) | 2014-04-30 |
| KR20110008047A (ko) | 2011-01-25 |
| US8193202B2 (en) | 2012-06-05 |
| CL2009000957A1 (es) | 2009-09-25 |
| AU2009239500A1 (en) | 2009-10-29 |
| IL208483A (en) | 2014-02-27 |
| CA2721919A1 (en) | 2009-10-29 |
| KR101706391B1 (ko) | 2017-02-13 |
| US8450332B2 (en) | 2013-05-28 |
| CO6321266A2 (es) | 2011-09-20 |
| CA2721919C (en) | 2016-08-16 |
| EA201071224A1 (ru) | 2011-06-30 |
| US20090264450A1 (en) | 2009-10-22 |
| IL208483A0 (en) | 2010-12-30 |
| MX2010011450A (es) | 2010-11-10 |
| AU2009239500B2 (en) | 2014-01-30 |
| EP2297153B1 (de) | 2015-05-27 |
| EP2297153A1 (de) | 2011-03-23 |
| TW200948814A (en) | 2009-12-01 |
| WO2009131940A1 (en) | 2009-10-29 |
| ZA201007129B (en) | 2011-12-28 |
| CN101565420B (zh) | 2015-05-20 |
| JP2011518189A (ja) | 2011-06-23 |
| CN101565420A (zh) | 2009-10-28 |
| KR20160129909A (ko) | 2016-11-09 |
| US20120329818A1 (en) | 2012-12-27 |
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